Background and aim: One strategy to stimulate bone regeneration is to support angiogenesis. One possible strategy is the use of the secretome of hypoxia-conditioned oral cells but there is no qualified protocol for the extraction of the secretome established yet. Aim of this study is to compare the secretome of oral cells conditioned with hypoxia and hypoxia mimetic agents (HMA) based on the concentration of vascular endothelial growth factor (VEGF) and the effects on osteoblastogenesis and osteoclastogenesis in vitro. In addition, it is unknown, if collagen membranes can be used as carrier materials for the secretome of hypoxia-conditioned oral cells. Furthermore, the release of the secretome from collagen barrier membranes is assessed. Materials and Methods: Secretome from oral fibroblasts derived from oral tissue such as gingiva, periodontal ligament and dental pulp (GF, PDLF, DPF) were cultivated under hypoxia and HMA (dimethyloxalylglycin, deferoxamine, L-mimosine). After 24 hours the secretome was collected and the cells were cultivated for another 24 hours. Collagen membranes were lyophilized with the secretome and then incubated in medium to evaluate the release based on VEGF. We measured the release of VEGF in the supernatants from the collagen membranes and the secretomes via immunoassays. In addition the effects of the supernantants on osteoblastogenesis and osteoclastogenesis were evaluated. Results: We found that hypoxia and HMA stimulated the secretion of VEGF in oral fibroblasts. Osteoblastogenesis was not influenced by the secretome compared to the control. Sek24h which contained DFO or L-MIM inhibited osteoclastogenesis. In addition, we showed that collagen membranes can be used as carriers for the secretome and that VEGF was released within three hours. Conclusion: Based on the results of our experiments hypoxia conditioning is an appropriate strategy to stimulate the secretion of VEGF in oral fibroblasts. Collagen membranes can be used as carriers for the secretome and they can release VEGF. It requires further studies to develope a personalized therapy to overcome compromised bone healing in patients with diabetes.